A chemical entity, which is potent in activity against its target, is the first step in the drug discovery process. However, a potent compound is only effective when an appropriate quantity is transported to the site of action at an acceptable rate after it has been administered. Even potent compounds benefit from optimization of these aspects. Many potent chemical entities do not have optimal pharmacokinetic parameters and hence the pharmacodynamic properties of these drugs are also suboptimal. In addition, there are several chemical entities that are already available in the market which have restricted pharmacokinetic properties and hence cannot be formulated in a manner convenient for patient administration.
The rate and extent of transportation into the blood circulation can be controlled by addition of certain groups to the original molecule, thereby modifying the molecule and its properties. Molecular modification is the chemical modification of a known and previously characterized lead compound for the purpose of enhancing its usefulness as a drug. This could mean enhancing its specificity for a particular target site, increasing its potency, improving its rate and extent of absorption, modifying the time course over which the active components become bio-available in the body (e.g., time release formulation), reducing its toxicity, and/or changing its physical or chemical properties (e.g., solubility) to optimize those aspects for particular applications.
However, the moiety used for molecular modification of the drug must be such that the therapeutic efficacy of the compound is retained and/or enhanced, while causing modification of the pharmacokinetic properties. Further, the modified compound, when administered, must not adversely affect the safety, toxicity and efficacy of the chemical entity beyond a tolerable degree.
The aforementioned strictures have resulted in limitations, some long standing, in the manner in which existing pharmaceuticals can be administered. For example, acetylsalicylic acid, the active ingredient in aspirin, is insufficiently soluble in saline to be administered intravenously. Hence, from the time it was discovered that chewing willow bark could reduce a fever, through the time aspirin was first compounded and till date, it is most frequently administered orally, and is not suitable for intravenous administration.
The strictures have also made it difficult to modify the pharmacodynamic properties of existing pharmaceuticals to optimize them for particular uses. Development of pharmaceuticals would be facilitated if it was possible to develop derivatization methods that could modify the pharmacokinetic and pharmacodynamic properties of a drug without detrimentally affecting a drug's efficacy, safety, and toxicity.
There is a need, as is illustrated by some of the examples shown herein, for a method of modifying chemical compounds that are useful as drugs such that one or more of their pharmacokinetic, physical, and/or pharmacodynamic properties are modified in the resultant compounds
Hence, to address this need, the present invention, aims to provide novel substituted methyl formyl based agents that may be used to modify existing compounds modify in terms of their pharmacokinetic, physical, and/or pharmacodynamic properties. The present invention discloses agents for modification and methods for using them to enhance particular properties while preserving the safety, toxicity, and efficacy of the original compound.